Challenges in mucosal vaccination of cattle

Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. The oral route is problematic in cattle and other ruminants where antigen degradation in the rumen is likely, prior to transit to the intestine. On the other hand, rumination can be exploited for exposure of nasopharyngeal tissues during cudding if vaccine antigen is expressed by a fibrous feed like alfalfa. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. Intranasal vaccination is an alternative approach for use in pre-ruminating calves. Intranasal administration of ISCOMs carrying soluble antigens of M. haemolytica, including native Lkt, induced Lkt specific IgA in nasal secretions after vaccination at 4 and 6 weeks of age. Subcutaneous (s.c.) administration of the same vaccine induced Lkt specific IgG in both serum and nasal secretions, whereas s.c. administration of a commercial M. haemolytica vaccine did not. Regardless of the vaccination strategy employed it is difficult to assess the immunogenicity of mucosally administered vaccines because production of secreted antibodies tends to be transient, and they do not persist on the mucosal surface in the absence of ongoing antigenic stimulation. An additional challenge is demonstration of vaccine efficacy in response to experimental infection. Protection of the mucosally vaccinated animal will most probably result from recall response, which may not amplify sufficiently to counter the effects of experimental pulmonary delivery of a large bolus of virulent bacteria, even though the response would suffice over the more prolonged and gradual infection that occurs in natural induction of pneumonia.